crossing96/oncoscreening huggingface dataset:
Sniffer mice discriminate urine odours of patients with bladder cancer: A proof-of-principle study for non-invasive diagnosis of cancer-induced odours.	"Similar to fingerprints, humans have unique, genetically determined body odours. In case of urine, the odour can change due to variations in diet as well as upon infection or tumour formation. We investigated the use of mice in a manner similar to ""sniffer dogs"" to detect changes in urine odour in patients with bladder cancer. We measured the odour discrimination thresholds of mice in a Y-maze, using urine mixtures from patients with bladder cancer (Stage I) and healthy volunteers (dietary variations) as well as occult blood- or antibiotic drug metabolite-modulated samples. Threshold difference indicated that intensities of urinary olfactory cues increase in the following order: dietary variation < bladder cancer < occult blood < antibiotic drug metabolites. After training with patient urine mixtures, sniffer mice discriminated between urine odours of pre- and post-transurethral resection in individual patients with bladder cancer in an equal-occult blood diluted condition below the detection level of dietary variations, achieving a success rate of 100% (11/11). Furthermore, genetic ablation of all dorsal olfactory receptors elevated the discrimination thresholds of mice by ≥ 10(5)-fold. The marked reduction in discrimination sensitivity indicates an essential role of the dorsal olfactory receptors in the recognition of urinary body odours in mice."	bladder
Knockdown of DUXAP10 inhibits proliferation and promotes apoptosis in bladder cancer cells via PI3K/Akt/mTOR signaling pathway.	DUXAP10 is a member of long non-coding RNAs (lncRNAs) and has been reported to be upregulated in bladder cancer (BC) tissues. However, the biological functions of DUXAP10 in BC are largely unknown. The present study detected the expression of DUXAP10 in human normal bladder cell SV‑HUC‑1 and BC cell lines. Subsequently, cell proliferation, cell cycle, and apoptosis were analyzed by knockdown of the DUXAP10 expression. Results suggested that the expression level of DUXAP10 was significantly enhanced in cancer cells. After knockdown of DUXAP10, cell proliferation was inhibited, cell cycle was arrested at G0/G1 phase, and apoptosis was increased in T24 and 5637 cells. Western blot analysis detected that knockdown of DUXAP10 decreased the expression of Bcl-xL, cyclin D and CDK4. This increased the expression of Bad, cleaved caspase‑3, cleaved caspase-9, and p27. Further studies indicated that knockdown of DUXAP10 inhibited PI3K/Akt/mTOR signaling pathway. Combining these results, our study suggests that DUXAP10 plays an important role in BC and DUXAP10 inhibition is a potential therapeutic target for BC.	bladder
Overexpression of exchange protein directly activated by cAMP-1 (EPAC1) attenuates bladder cancer cell migration.	Exchange protein directly activated by cAMP (EPAC) is a mediator of a cAMP signaling pathway that is independent of protein kinase A. EPAC has two isoforms (EPAC1 and EPAC2) and is a cAMP-dependent guanine nucleotide exchange factor for the small GTPases, Rap1 and Rap2. Recent studies suggest that EPAC1 has both positive and negative influences on cancer and is involved in cell proliferation, apoptosis, migration and metastasis. We report that EPAC1 and EPAC2 expression levels were significantly lower in bladder cancer tissue than in normal bladder tissue. In addition, bladder cancer cell lines showed reduced EPAC1 mRNA expression. Furthermore, EPAC1 overexpression in bladder cancer cell lines induced morphologic changes and markedly suppressed cell migration without affecting cell viability. The overexpressed EPAC1 preferentially localized at cell-cell interfaces. In conclusion, reduced EPAC1 expression in bladder tumors and poor migration of EPAC1-overexpressing cells implicate EPAC1 as an inhibitor of bladder cancer cell migration.	bladder
[Supplementary optical techniques for the detection of nonmuscle invasive bladder cancer].	White light cystoscopy (WL) is the gold standard for the detection of bladder cancer. It can be performed using a rigid or flexible urethrocystoscope. With the more recent introduction of high definition (HD) techniques, WL cystoscopy has been decisively improved. Supplementary optical techniques are also used to improve the detection of bladder cancer. Among these are photodynamic diagnosis (PDD), narrow-band imaging (NBI), S‑technologies of IMAGE1 S, optical coherence tomography (OCT), confocal laser endomicroscopy (CLE), and Raman spectroscopy. The aim of the present work is to introduce the techniques and to discuss their current role and future potential in the detection of bladder cancer.	bladder
Perioperative morbidity, bowel function and oncologic outcome after radical cystectomy and ileal orthotopic neobladder reconstruction: Studer-pouch versus I-pouch.	OBJECTIVE: To investigate whether the length of ileum used for ileal orthotopic neobladder (ONB) reconstruction (60 cm vs. 40 cm) after radical cystectomy (RC) for bladder cancer (BC) impacts on bowel function, postoperative complications or survival outcome. MATERIAL AND METHODS: In this retrospective study, we included 56 patients who received an ONB (Studer (S)-Pouch: 23 patients; I-Pouch: 33 patients) after RC for BC between 2003 and 2011. Preoperative comorbidities were assessed by the Charlson Comorbidity Index (CCI) and surgical complications as graded by the Clavien-Dindo classification. Changes of perioperative bowel habits were retrospectively evaluated by the validated Gastrointestinal Quality of Life Index (GIQLI). Kaplan-Meier analyses calculated survival outcomes between both ONB types. RESULTS: Preoperative CCI was comparable between S- and I-pouch patients. No significant differences were observed for 30-day major- (p = 0.33) and minor (p = 0.96) complication rates between both neobladder types. S-Pouch patients reported higher preoperative stool frequencies (S-pouch: mean 2.7; I-pouch: mean 3.4; p = 0.049) and tended to suffer from urgency (S: mean 2.9; I: mean 3.4; p = 0.059). No significant differences in postoperative bowel disorders were found between both neobladder types (S-Pouch: 15.9, IQR; I-Pouch: 16.6 IQR; p = 0.84). Furthermore, we observed no overall-, cancer specific- or recurrence free survival advantage for either of both ONB variants (p = 0.81; 0.65 and 0.78), respectively. CONCLUSION: Comorbidities, perioperative complication rates and bowel habits were similar between both ONB substitutes and did not influence survival outcomes. These stratified data suggest that the length of ileum used for ONB reconstruction (60- vs. 40 cm) does not impact per se on postoperative bowel function.	bladder
[Fever, Hepatic Dysfunction and Interstitial Pneumonia Caused by Intravesical Bacillus Calmette-Guerin (BCG) Instillation after Urethral Bougie : A Case Report].	A 60-year-old man had a past history of urothelial carcinoma of the left renal pelvis treated with laparoscopic left total nephroureterectomy in October 2004. He underwent transurethral resection of the bladder tumor (TUR-Bt) twice for recurrence of urothelial carcinoma in the bladder in April 2014 and February 2015, and subsequently received intravesical Bacillus Calmette-Guerin (BCG) instillation at weekly intervalsfor prevention of recurrence. In November 2016, a year and a half after BCG induction, he received BCG therapy after urethral bougie to dilate the urethral stricture. After BCG therapy, he exhibited a continuously high fever. Immediate antituberculosis drug therapy in consideration of BCG sepsis failed to improve the symptoms, and all cultures from urine and blood were negative for mycobacterium tuberculosis. Serum liver enzyme was markedly elevated and chest CT showed diffuse interstitial shadows in both lower lungs. Thus, we considered that these symptoms were caused by a hypersensitivity reaction to BCG and started pulse steroid therapy. After pulse steroid therapy, body temperature, and hepatic function became normal and interstitial pneumonia subsided.	bladder
Availability and Patterns of Intravesical BCG Instillations.	PURPOSE: Intravesical BCG instillations improve recurrence free survival in patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: This is a national survey study, covering 223 urological centres, aimed at reliable identification of BCG availability and implemented treatment patterns. RESULTS: Response rate was 93.7%. BCG was used in 56.5% of urological departments. Another 22.7% referred patients to other hospitals for instillations, while 20.8% did not recommend BCG at all. The most common indications for BCG instillations were as follows: T1 tumours (88.5%), carcinoma in situ (83.6%) and high grade tumours (73.8%). Maintenance therapy was routinely abandoned in 16.4% of centres or was scheduled for <1 year, 1 year, 3 years and 1-3 years in 6.6%, 19.7%, 21.3% and 31.2% of centres, respectively. Continuation of BCGdespite treatment failure in carcinoma in situ cases was considered in 21.3% of departments. CONCLUSION: Our findings indicate that BCG is underused, while patterns of maintenance and follow-up are suboptimal.	bladder
Purified protein derivative skin test reactions are associated with clinical outcomes of patients with nonmuscle invasive bladder cancer treated with induction bacillus Calmette-Guérin therapy.	OBJECTIVES: To investigate the relationship between purified protein derivative (PPD) skin test reactions before bacillus Calmette-Guérin (BCG) therapy and the clinical outcomes of BCG-naïve nonmuscle invasive bladder cancer patients treated with adjuvant BCG therapy. MATERIALS AND METHODS: A total of 288 nonmuscle invasive bladder cancer patients subjected to the PPD skin test before BCG therapy were included. PPD skin test reactions were categorized into 3 groups: positive, slightly positive, and negative. The presence of an induration was positive. If an induration was absent, erythema of 10mm or more and less than 10mm corresponded to slightly positive and negative, respectively. RESULTS: A total of 66 (22.9%), 149 (51.7%), and 73 (25.3%) patients exhibited a positive, slightly positive, and negative to PPD skin test, respectively. The 5-year recurrence-free survival rate of patients with positive PPD skin test reactions was 89.4 ± 4.1%, which was significantly higher than those of patients with slightly positive (65.5 ± 4.2%, P = 0.001) and negative reactions (56.4 ± 6.6%, P<0.001). A multivariate Cox regression analysis revealed that a positive PPD skin test reaction was independently associated with tumor recurrence (hazard ratio of 0.233, P<0.001), but not with stage progression. The incidence of fever persisting for more than 2 days or fever of ≥38°C was significantly higher in patients with a positive PPD skin test reaction (18.2%) than in patients with slightly positive (8.7%) and negative PPD skin test reactions (4.1%). CONCLUSIONS: The PPD skin test reactions before BCG therapy may predict clinical outcomes following BCG therapy and help clinicians counsel patients exhibiting strong therapeutic effects with BCG therapy and potentially major BCG-related side effects.	bladder
Bladder Cancer: Diagnosis and Treatment.	Bladder cancer is the sixth most prevalent malignancy in the United States and causes more than 16,000 deaths annually. The most common clinical presentation is asymptomatic hematuria, which should prompt evaluation with cystoscopy, renal function testing, and upper urinary tract imaging in adults 35 years and older and in those with irritative voiding symptoms, risk factors for bladder cancer, or gross hematuria at any age. Transurethral resection of the bladder tumor allows for definitive diagnosis, staging, and primary treatment. Non-muscle-invasive disease is treated with transurethral resection, most often followed by intravesical bacille Calmette-Guérin or intravesical chemotherapy. Bladder cancer that invades the muscle layer is typically treated with radical cystectomy and neoadjuvant chemotherapy because of higher rates of progression and recurrence. No major organization recommends screening asymptomatic adults for bladder cancer, and the U.S. Preventive Services Task Force concluded that current evidence is insufficient to assess the balance of benefits and harms of screening.	bladder
High neutrophil-to-lymphocyte ratio predicts worse overall survival in patients with advanced/metastatic urothelial bladder cancer.	OBJECTIVES: To study the role of the neutrophil-to-lymphocyte ratio in predicting survival outcomes for patients with advanced bladder cancer. METHODS: We retrospectively reviewed 150 patients diagnosed with advanced or metastatic bladder cancer between January 2004 and June 2014. The neutrophil-to-lymphocyte ratio was computed on diagnosis and after the first cycle of chemotherapy. A neutrophil-to-lymphocyte ratio cut-off of 3.0 was determined, with a concordance index of 0.89. Kaplan-Meier curves, log-rank tests, Cox proportional hazards and logistic regression models were used to predict the association of the neutrophil-to-lymphocyte ratio with survival outcomes. RESULTS: Just five patients were alive at the end of the study; the rest died from metastatic bladder cancer. On multivariate analysis, higher Eastern Cooperative Oncology Group status, lymphadenopathy, visceral metastases and neutrophil-to-lymphocyte ratio ≥3.0 were associated with poorer overall survival (hazard ratio 1.67, P = 0.03; hazard ratio 1.97, P = <0.01; hazard ratio 2.02, P = <0.01; hazard ratio 5.06, P = <0.01), whereas chemotherapy conferred better overall survival (hazard ratio 0.546, P = 0.01). Furthermore, the role of chemotherapy prolonged survival longer in patients with a neutrophil-to-lymphocyte ratio <3.0 (median overall survival 13.0 vs 22.0 months, hazard ratio 0.273, P = 0.008) compared with a neutrophil-to-lymphocyte ratio ≥3.0 (median overall survival 4.0 vs 7.0 months, hazard ratio 0.452, P = 0.020). More importantly, when dichotomized to the four different pre- and post-chemotherapy groups, patients with a pre- and post-chemotherapy neutrophil-to-lymphocyte ratio <3.0 had the best additional median overall survival of 19.0 months compared with patients with a pre- and post-chemotherapy neutrophil-to-lymphocyte ratio ≥3.0 (3.0 months). CONCLUSIONS: Elevated neutrophil-to-lymphocyte ratio is independently associated with poorer chemotherapeutic response and overall survival in patients with advanced or metastatic bladder cancer. The neutrophil-to-lymphocyte ratio can be an inexpensive novel factor in prognosticating disease progression and providing better patient counseling.	bladder
Long-term Outcomes from Re-resection for High-risk Non-muscle-invasive Bladder Cancer: A Potential to Rationalize Use.	BACKGROUND: Guidelines advocate early re-resection for these cancers, although the benefits are unclear and the uniform need is questioned. Here, we compare the outcomes using a large single-center cohort. OBJECTIVES: To compare the outcomes of patients with high-grade non-muscle-invasive bladder cancer (BC) who underwent and who did not undergo re-resection following their initial treatment. DESIGN, SETTING, AND PARTICIPANTS: We identified all eligible patients with a new diagnosis treated between 1994 and 2009 in Sheffield. We annotated these with hospital and registry records. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcomes were disease-specific and overall survival. Secondary outcomes were the findings at re-resection, rates of muscle invasion, and radical treatment. Statistical tests were two tailed and significance defined as p<0.05. RESULTS AND LIMITATIONS: We identified 932 eligible patients, including 229(25%) who underwent re-resection within 12 wk and 234 (25%) within 3-6 mo after diagnosis. Clinicopathological criteria were similar in patients with and without re-resection. Histological findings on re-resection were no residual cancer in 91 (20%) and BC in 138 (30%: 15 low-grade and 85 high-grade non-muscle-invasive cancers, and 38 muscle-invasive cancers). Patients with re-resection were more frequently diagnosed with muscle invasion (126 [27%] vs 49 [11%], chi-square p<0.001) and more commonly underwent radical treatment (127 [27%] vs 35 [8%], p<0.001) than those without re-resection. A total of 207 patients died from BC, including 46 (22%) with and 161 (78%) without re-resection. Patients who underwent re-resection within 3 mo had significantly higher disease-specific (log rank p=0.009) and overall survival (p<0.001) survival compared with those who did not. Differences were present only for patients with pT1 cancer at diagnosis. CONCLUSIONS: Patients undergoing re-resection within 3 mo of diagnosis were more likely to have histologically identified muscle invasion, were more likely to undergo radical treatment, and had a higher survival rate. The differences were greatest in patients with lamina propria invasion, suggesting the potential to avoid in others. Limitations of our work include retrospective design and selection bias. PATIENT SUMMARY: Patients undergoing re-resection after a diagnosis of high-grade non-muscle-invasive bladder cancer had higher disease-specific and overall survival rates due to more accurate diagnosis and appropriate subsequent radical treatment. Re-resection carries greatest benefit to patients with lamina propria invasion at diagnosis.	bladder
Inhibition of REDD1 Sensitizes Bladder Urothelial Carcinoma to Paclitaxel by Inhibiting Autophagy.	Purpose: Regulated in development and DNA damage response-1 (REDD1) is a stress-related protein and is involved in the progression of cancer. The role and regulatory mechanism of REDD1 in bladder urothelial carcinoma (BUC), however, is yet unidentified.Experimental Design: The expression of REDD1 in BUC was detected by Western blot analysis and immunohistochemistry (IHC). The correlation between REDD1 expression and clinical features in patients with BUC were assessed. The effects of REDD1 on cellular proliferation, apoptosis, autophagy, and paclitaxel sensitivity were determined both in vitro and in vivo Then the targeted-regulating mechanism of REDD1 by miRNAs was explored.Results: Here the significant increase of REDD1 expression is detected in BUC tissue, and REDD1 is first reported as an independent prognostic factor in patients with BUC. Silencing REDD1 expression in T24 and EJ cells decreased cell proliferation, increased apoptosis, and decreased autophagy, whereas the ectopic expression of REDD1 in RT4 and BIU87 cells had the opposite effect. In addition, the REDD1-mediated proliferation, apoptosis, and autophagy are found to be negatively regulated by miR-22 in vitro, which intensify the paclitaxel sensitivity via inhibition of the well-acknowledged REDD1-EEF2K-autophagy axis. AKT/mTOR signaling initially activated or inhibited in response to silencing or enhancing REDD1 expression and then recovered rapidly. Finally, the inhibited REDD1 expression by either RNAi or miR-22 sensitizes BUC tumor cells to paclitaxel in a subcutaneous transplant carcinoma model in vivoConclusions: REDD1 is confirmed as an oncogene in BUC, and antagonizing REDD1 could be a potential therapeutic strategy to sensitize BUC cells to paclitaxel. Clin Cancer Res; 24(2); 445-59. ©2017 AACR.	bladder
Synthetic regulatory RNAs selectively suppress the progression of bladder cancer.	The traditional treatment for cancer is lack of specificity and efficacy. Modular synthetic regulatory RNAs, such as inhibitive RNA (iRNA) and active RNA (aRNA), may overcome these limitations. Here, we synthesize a new iRNA to bind the upstream activating sequence (UAS) of a minimal promoter that drives expression of artificial miRNAs (amiRNAs) targeting MYC, which represses the binding interaction between UAS and GAL4 fusion protein (GAL4-VP64) in GAL4/UAS system. The aRNA driven by a tumor-specific mutant human telomerase reverse transcriptase (hTERT) promoter is created to interact with iRNA to expose UAS again in bladder cancer. Without the aRNA, mRNA and protein levels of MYC, cell growth, cell apoptosis and cell migration were no significance in two bladder cancer cell lines, T24 and 5637, and human foreskin fibroblast (HFF) cells. The aRNA significantly inhibited the expression of MYC in mRNA and protein levels, as well as the proliferation and migration of the cancer cells, but not in HFF cells. These results indicated that regulatory RNAs selectively controlled the expression of amiRNAs and ultimately suppress the progression of bladder cancer cells without affecting normal cells. Synthetic regulatory RNAs might be a selective therapeutic approach for bladder cancer.	bladder
[Mechanism in growth inhibition of quercetin on human bladder cancer cell line].	To investigate the inhibitory mechanism of quercetin on growth of human bladder cancer cell line(BIU-87). BIU-87 cells were cultured in vitro, and co-cultured with varying concentrations of quercetin, and the anti-proliferative activity was determined by CCK-8 assay. Apoptosis of quercetin-induced BIU-87 cells and cell cycle were determined by flow cytometry analysis. Expressions of Bal-2 and Bal-xL, and related proteins in TAK1/JNK signal pathway were measured using Western blot analysis. After treatment with quercetin for 24 h and 48 h, the proliferation of BIU-87 cells was significantly suppressed in a dose-dependent manner according to CCK-8 assay(P<0.05). The flow cytometry analysis indicated that each group of quercetin leads to a significant higher percentage of apoptosis of BIU-87 cells than control group after treatment with quercetin for 24 h and 48 h; In G₀/G₁ period, cells reduced, while the amount of cells in G₂/M period increased, and cells in S period remained the same amount. Expressions of Bal-2, Bal-xL, p-TAK1, p-MKK4/7, p-JNK decreased in BIU-87 cells after treatment with quercetin. Quercetin could inhibit the proliferation and promote the apoptosis of BIU-87 cells. The mechanism may be correlated with the inhibition of TAK1/JNK signaling pathway, which led to the further decrease in expressions of Bal-2 and Bal-xL.	bladder
Update of systemic immunotherapy for advanced urothelial carcinoma.	PURPOSE: Until recently, therapeutic options for metastatic urothelial carcinoma (UC) were limited to cytotoxic chemotherapy. Cisplatin-based combination chemotherapy has proven benefit in the perioperative settings for muscle-invasive disease and for metastatic disease. A large proportion of patients is cisplatin-ineligible and limited to less effective chemotherapeutic options. However, treatment options have recently expanded with the development of systemic immunotherapy with checkpoint inhibitors (CPIs).Herein we review the clinical trial data supporting the use of CPIs in UC. We also describe ongoing clinical trials that are exploring CPIs in novel combinations and in a variety of disease settings. METHODS: A comprehensive literature review was performed using Medline/Pubmed and clinical trials. RESULTS/CONCLUSIONS: Based on results of the IMvigor 210 clinical trial, the anti-programmed death-ligand1 antibody atezolizumab gained regulatory approval in May 2016 for use in locally advanced and metastatic UC in patients with progression of disease despite prior platinum-based chemotherapy. Since that time, additional CPIs (avelumab, durvalumab, nivolumab, and pembrolizumab) have gained regulatory approval in the postplatinum setting. The approval of pembrolizumab was supported by KEYNOTE-045, the first reported randomized, phase III trial of a CPI in UC. Atezolizumab and pembrolizumab are also approved for first-line therapy for cisplatin-ineligible patients with locally advanced or metastatic disease. The rapid expansion of therapeutic options in UC has shifted the treatment paradigm.	bladder